Changes in the osmolality of body fluids (changes as minor as 1% are sufficient) play the most important role in regulating AVP secretion. The receptors that monitor changes in osmolality of body fluids (termed osmoreceptors) are distinct from the cells that synthesize and secrete AVP, and are located in the organum vasculosum of the lamina terminalis (OVLT) of the hypothalamus.
The osmoreceptors sense changes in body fluid osmolality by either shrinking or swelling. Recent studies have provided evidence that transient receptor potential vanilloid (TRVP) cation channels are involved in the response of the cells to changes in body fluid osmolality. The osmoreceptors respond only to solutes in plasma that are effective osmoles (see ). For example, urea is an ineffective osmole when the function of osmoreceptors is considered. Thus elevation of the plasma urea concentration alone has little effect on AVP secretion.
When the effective osmolality of the plasma increases, the osmoreceptors send signals to the AVP synthesizing/ secreting cells located in the supraoptic and paraventricular nuclei of the hypothalamus, and AVP synthesis and secretion are stimulated. Conversely, when the effective cAngiotensin II also stimulates AVP secretion; the cells that mediate this response are located in the subfornical organ (SFO).
The gene for AVP is found on chromosome 20. It contains approximately 2000 base pairs with three exons and two introns. The gene codes for a preprohormone that consists of a signal polypeptide, the AVP molecule, neurophysin, and a glycopeptide (copeptin). As the cell processes the preprohormone the signal peptide is cleaved off in the rough endoplasmic reticulum. Once packaged in neurosecretory granules, the preprohormone is further cleaved into AVP, neurophysin, and copeptin molecules. The neurosecretory granules are then transported down the axon to the posterior pituitary and stored in the nerve endings until released. When the neurons are stimulated to secrete AVP, the action potential opens Ca++ channels in the nerve terminal, which raises the intracellular [Ca++] and causes exocytosis of the neurosecretory granules. All three peptides are secreted in this process. Neurophysin and copeptin do not have an identified physiological function.
osmolality of the plasma is reduced, secretion is inhibited. Because AVP is rapidly degraded in the plasma, circulating levels can be reduced to zero within minutes after secretion is inhibited. As a result the AVP system can respond rapidly to fluctuations in body fluid osmolality.
Fig. 35.4A illustrates the effect of changes in plasma osmolality on circulating AVP levels. The slope of the relationship is quite steep and accounts for the sensitivity of this system. The set point of the system is the plasma osmolality value at which AVP secretion begins to increase. Below this set point, virtually no AVP is released. The set point varies
CHAPTER 35 Control of Body Fluid Osmolality and Volume among individuals and is genetically determined. In healthy adults it varies from 275 to 290 mOsm/kg H2O (average ≈ 280–285 mOsm/kg H2O). Several physiological factors can also change the set point in a given individual. As discussed later, alterations in blood volume and pressure can shift it. In addition, pregnancy is associated with a decrease in the set point. The mechanism responsible for the set-point shift with pregnancy is not completely understood but is likely due to hormone levels (e.g., relaxin and chorionic gonadotropin) that are elevated during pregnancy.
Hemodynamic (Nonosmotic) Control of AVP Secretion